Int. J. Mol. Sci. 2012, 13(2), 1497-1511; doi:10.3390/ijms13021497
Review

Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

* email, email and email
Received: 6 September 2011; in revised form: 12 January 2012 / Accepted: 13 January 2012 / Published: 1 February 2012
(This article belongs to the Special Issue Advances in Molecular Diagnostics)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.
Keywords: hemochromatosis; primary iron overload; HFE; high-resolution melting; HJV; molecular diagnostic
PDF Full-text Download PDF Full-Text [204 KB, uploaded 19 June 2014 04:11 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Santos, P.C.J.L.; Krieger, J.E.; Pereira, A.C. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis. Int. J. Mol. Sci. 2012, 13, 1497-1511.

AMA Style

Santos PCJL, Krieger JE, Pereira AC. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis. International Journal of Molecular Sciences. 2012; 13(2):1497-1511.

Chicago/Turabian Style

Santos, Paulo C. J. L.; Krieger, Jose E.; Pereira, Alexandre C. 2012. "Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis." Int. J. Mol. Sci. 13, no. 2: 1497-1511.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert